Arginine is an amino acid to be a direct substrate of nitric oxide (NO) synthase. Moreover, it is an intermediate in the urea cycle in the liver, and plays an important role in detoxication of ammonia produced in the body. As its physiological actions, vasodilation due to oral ingestion of arginine (non-patent document 1), suppression of blood pressure increase (non-patent document 2), improvement of sexual function (non-patent document 3) and the like have been reported.
In addition, arginine is known to have a growth hormone secretory action (non-patent document 4). Since the growth hormone has an action to promote protein synthesis, sugar metabolism, lipid metabolism and the like, ingestion of arginine is expected to provide a muscle synthesis action and a wound healing action. In addition, there are many effects exerted by oral ingestion by animals and human, such as ammonia detoxication (non-patent document 5), immunostimulation (non-patent document 6), insulin secretion (non-patent document 7), polyamine synthesis action (non-patent document 8) and the like.
Thus, enhancement of the arginine level of the body is considered to be useful for maintenance of health and improvement of disease condition. In fact, arginine is ingested in the form of pharmaceutical products, functional foods and the like with an expectation of such effects.
On the other hand, citrulline is not used as a starting material for the synthesis of protein in the body, and is one kind of amino acid present in a free form. In the body, citrulline plays an important role as an arginine precursor for arginine biosynthesis or a constituent factor of NO cycle relating to NO supply.
It is known that orally ingested citrulline is mostly converted to arginine in the kidney and arginine is efficiently supplied systemically (non-patent document 9). To increase blood arginine level, ingestion of citrulline is reported to be more effective than ingestion of arginine itself (non-patent document 10). In addition, it is reported that ingestion of citrulline and arginine in combination enhances NO production and strengthen an anti-arteriosclerosis action, rather than individual ingestion of each (non-patent document 11). However, these are effects provided by long-term ingestion.
On the other hand, among the effects expected to result in prevention or improvement by the enhancement of the blood arginine level, appearance of effect in a short time after ingestion is desired in temporary symptoms caused by decreased blood flow, such as sensitivity to coldness, swelling, stiff shoulders, erectile dysfunction and the like, muscle fatigue due to accumulation of ammonia after exercise and the like. However, an oral preparation that rapidly and effectively increases blood arginine level after ingestion is not known.    non-patent document 1: “Journal of the American College of Cardiology”, 2000, vol. 35, p. 706-713    non-patent document 2: “Laboratory Investigation”, 1993, vol. 68, p. 174-184    non-patent document 3: “BJU International”, 1999, vol. 83, p. 269-273    non-patent document 4: “Journal of Laboratory & Clinical Medicine”, 2000, vol. 135, p. 231-237    non-patent document 5: “New England Journal of Medicine”, 1957, vol. 256, p. 941-943    non-patent document 6: “Surgery”, 1990, vol. 108, p. 331-336, 336-337    non-patent document 7: “Journal of Clinical Investigation”, 1966, vol. 45, p. 1487-1502    non-patent document 8: “Nutrition”, 1999, vol. 15, p. 563-569    non-patent document 9: “Amino acids”, 2005, vol. 29, p. 177-205    non-patent document 10 “Gut”, 2004, vol. 53, p. 1781-1786    non-patent document 11: “PNAS” 2005, vol. 102, p. 13681-13686